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Vaping and Disease Risks
Cynthia Grondin, PhDComparative Toxicogenomics Database
North Carolina State University11/12/2019
e-liquid
mouthpiece
on/off switch
Lithium battery
atomizer
Vape mods
aerosol/vapor
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
common e-cigarette vaping devices
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Juuls – “Juuling”
1 pod = nicotine in entire pack of cigarettes
ALL Juuls contain NICOTINE
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Anatomy of a Juul
mouthpiece
chimney
gold plated contact
coil, wick
indicator
e-liquid
battery
e-vapor
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Beyond the List of Ingredients
nicotinepropylene glycolglycerinbenzoic acidflavorings, oils
Juul chemicals
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
biotransformation of nicotine into other compounds
Pharmacological Reviews 57(1):79–115
nicotinepropylene glycolglycerinbenzoic acidflavorings, oils
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
conversion of propylene glycol into acetaldehyde and formaldehyde (carcinogens)
Environ Sci Technol 50(17):9644-9651
Juul chemicals
Beyond the List of Ingredients
nicotinepropylene glycolglycerinbenzoic acidflavorings, oils
conversion of glycerin into acrolein (carcinogen)
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Environ Sci Technol 50(17):9644-9651
Juul chemicals
Beyond the List of Ingredients
nicotinepropylene glycolglycerinbenzoic acidflavorings, oils
glycerol
propylene glycol
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
PLoS ONE 12(3):e0173055
benzoic acid can transform into benzene (carcinogen)Juul chemicals
Beyond the List of Ingredients
nicotinepropylene glycolglycerinbenzoic acidflavorings, oils
1-hexanol cyclotene limonene
2,3-pentanedione decan-4-olide linalool
2,5-dimethylpyrazine decanaldehyde linalyl acetate
2,6-lutidine Diacetyl maltol
2-acetylpyrrole diethyl succinate Menthol
3,4-dihydrocoumarin ethyl acetoacetate menthone
3-hexen-1-ol ethyl hexanoate methyl acetate
4-Butyrolactone ethyl lactate methyl cinnamate
5-methyl-2-furfural ethyl maltol methyl salicylate
acetoin Ethyl Salicylate methylheptenone
alpha-terpineol ethyl vanillin Nicotine
anisyl acetate Eucalyptol n-pentanol
benzaldehyde Eugenol Pulegone
benzyl acetate Furaldehyde pyridine
Benzyl Alcohol furaneol raspberry ketone
Camphor furfuryl alcohol tetramethylpyrazine
Cinnamaldehyde gamma-valerolactone vanillin
citronellol isoamyl acetate
Alien Blood Double Apple Hookah Oatmeal Cookie
Bad Apple Energy Drink Orange Mint
Bluewater Punch Grape Hookah Peach Schnapps
Carmel Popcorn Iced Berry Pina Colada
Cherry Lava Java Jolt Pomegranate
CooCoo Coconut Just Guava Snap!
Cotton Candy Kick! Tutti Frutti
Cupcake Menthol Vanilla Bean
flavorings may contain many other chemicals such as Diacetyl(shown to cause Popcorn Lung)
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Juul chemicals
Beyond the List of Ingredients
Universal System for Analysis of Vaping (U-SAV) machine
What chemicals are in e-liquids and aerosols?
Int J Environ Res Public Health 14(10): 1225
chemicals are measured in e-liquids, aerosols, urine, blood, saliva
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Vaping is NOT just inhaling flavored water vapor
PLoS One. 2013;8(3):e57987
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Metals contaminate e-liquids and aerosols
Environ Health Perspect. 2018 Feb 21;126(2):027010
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
propylene glycol
glycerol
benzoic acid
glycerin
benzeneacrolein
glycidol
propionaldehyde
1-hexanol
anisyl acetategamma-valerolactone
5-methyl-2-furfural
4-butyrolactone
acetoin
decanaldehyde
methylheptanone
maltol
Eugenolethyl acetoacetate
2,3-pentanedionedecanaldehyde
furaldehyde
limonene
benzyl acetate
Menthol
cyclotene
Diacetyl
vanillin
1-hexanol3,4-dihydrocourmarin
methyl salicylate
Pulegone
camphor
alpha-terpineol
3-hexen-1-ol
pyridine
2-acetylpyrrole
2,6-lutidine
Nicotine
Free Radicals
methylglyoxal
2-butenal
Particulate Matter
Acetone Acetaldehyde
Formaldehyde
Aluminum
Nickel
Lead
ZincManganese
Tin
Chromium
Copper
Iron
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Vaping aerosols contain MANY chemicalsmany more than shown here
Diseases
Chemicals
Genes
GO &
Phenotype
Comparative Toxicogenomics
Database (CTD)
Integrate data
Exposures
Pathways
ctdbase.org
• >43 million
toxicogenomic
relationships
• updated monthly
Cellular locationMolecular functionBiological processes
PhD-level scientists
read studies
Health Effects of Chemicals
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
ctdbase.org
Chemicals Diseasesdirect
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
ctdbase.org
Chemicals Diseases
Genes
inferred
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Nicotine (Protonated) vs Nicotine (Free base) vs Salts
Nic[H+] Nic
• acidic environment low pH• protonated• does not cross membranes
rapidly• less potent• deposits in respiratory tract
~50% efficiency• tobacco smoke • ~ 12mg/cigarette
• deprotonated/free base• more volatile• more potent• harsher throat hit• increased sensory effects• rapidly deposits in mouth,
respiratory tract• e-cigarettes• ~0-24 mg/ml
Nicotine Salts
• nicotine benzoate• nicotine levulinate• nicotine pyruvate• rapid absorption
• JUULs• smoother throat hit
• allows higher nicotine
• ~60 mg/ml
flavors can affect pH of e-liquids and consequently, nicotine form
+
-
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Effects of Nicotine in e-cigarette aerosol
interacts with 1,128 unique genes
Nicotine
involved in 2,656 gene interactions
involved in 631 molecular pathways
associated with 934 phenotypes
directly related to 224 diseases
inferred relationship to 1,837 diseases
Cynthia J Grondin, PhD 11/12/2019Illuminating how chemicals affect human health
Comparative Toxicogenomics Database
Nicotine Effects on HealthNicotine-DiseasesNicotine-Disease Categories
• Cardiovascular Disease• Respiratory Tract Diseases• Reproductive Disorders• Depression• Lung Cancer• Colon Cancer• Type 2 Diabetes• Pulmonary Fibrosis• Pancreatic Cancer• Heart Attack• Nerve Degeneration• Atherosclerosis• Stroke• Metastasis• Acute Kidney Injury• Hypertension• Panic Disorder
224 direct/1837 inferred disease relationships
Cynthia J Grondin, PhD 11/12/2019Illuminating how chemicals affect human health
Comparative Toxicogenomics Database
Chemical-Disease Associations in CTD
Input chemicals in e-liquids/aerosols
Search for disease associations
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Chemicals in Juul pods and aerosols
• Nervous System • Cardiovascular • Respiratory Tract
• Cancer• Immune System• Mental Disorders
Top Disease Categories
Cynthia J Grondin, PhD 11/12/2019Illuminating how chemicals affect human health
Comparative Toxicogenomics Database
Vaping-Related Illness aired on GMA 9/3/2019
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Cynthia J Grondin, PhD 11/12/2019Illuminating how chemicals affect human health
Comparative Toxicogenomics Database
Number of Lung Injury Cases Reported to CDC as of November 5, 2019
Centers for Disease Control Updates
November 8, 2019
• 2,051 vaping-related illnesses across 49 states
• 39 confirmed deaths related to vaping, in 24 states
• more deaths under investigation
• chemical of concern vitamin E acetate
October 15, 2019 (867 patients)
• 86% reported vaping THC (34% THC exclusively)
• 64% reported vaping nicotine (11% nicotine exclusively)
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Scientific Study on Vaping Cannabis
• cannabis smoke contains many of the same carcinogens found in
tobacco smoke
• average particle concentrations of 200-600 ug/m3, peak concentrations
1600 mg/m 3
• equivalent to extreme air pollution (wildfires and severe industrial
pollution)
• can cause cardiovascular and respiratory disease
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Measuring Aerosol Particulate Emissions from Cannabis Vaporization and Dabbing
Jacques PA, Zalay M, Huang A, Jee K, Schick S [email protected]
Vaping THC - Concerns
1) Pesticides and Solvents
i. pesticides and fungicides used to grow cannabis
ii. concentration solvents (butane, hexane, isobutene, isopropyl alcohol)
2) Flavorings added to cannabis products
i. Diacetyl, 2,3-Pentanedione, Acetoin
3) Cutting agents
i. Vitamin E acetate
Borodovsky JT. Addiction http://doi.org/10.1111.add.14855
Cynthia J Grondin, PhD 11/12/2019Illuminating how chemicals affect human health
Comparative Toxicogenomics Database
Vitamin E Analogues
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
I II III
functional group
signalingdomain
hydrophobic domain
a-Tocopheryl Acetate
Br J Cancer. 2003. 88: 1948-1955
THC Effects on HealthTHC-Disease AssociationsTHC-Disease Categories• Substance-related Disorders• Nerve Degeneration• Morphine Dependence• Bipolar disorder• Marijuana Abuse• Acute Kidney Injury• Anxiety Disorders• Hypotension• Cognition Disorders• Opioid Disorders• Pregnancy Complications• Movement Disorders• Memory Disorders• Learning Disorders• Tachycardia• Catalepsy• Pulmonary Edema
87 direct/2874 inferred disease relationships
Cynthia J Grondin, PhD 11/12/2019Illuminating how chemicals affect human health
Comparative Toxicogenomics Database
e-cig vapor S. mutans
Kim et al. PLoS One 2018 Sept 7
Vaping Effects on Teeth
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
More Immediate Effects?
Nicotine is HIGHLY addictive
Increases likelihood of smoking cigarettes
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Acrolein, nicotine and other vaping chemicals may contribute to a hardening of the arteries and limit cardiovascular fitness
Effects on Cardiovascular Fitness:
More Immediate Effects?
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Effects on Mental Health:Adolescent e-cigarette users show increased Depression, Panic Disorder and inability to experience pleasure vs. non-users
More Immediate Effects?
Vaping associated with illicit drug use, mental health problems and impulsivity in university students
Leventhal AM et al. J Psychiatr Res. 2016 FebGrant JE et al. Ann Clin Psychiatry 2019 Feb
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Effects on Sexual Health:
Nicotine can significantly decrease physiological sexual arousal in healthy nonsmoking men and women (18-22 years)
More Immediate Effects?
J Sex Med. 2008 Jan;5(1):110-21J Sex Med. 2008 May; 5(5):1184-1197
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Chen et al., J Expo Sci Environ Epidemiol. 2017 Dec 29
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Second-hand and Third-hand Vape
Vaping Affects Users Differently
• type of device
• e-liquid
• vaping patterns
• coil resistance, age, composition
• user age, weight, metabolism, health,
genetics
• environmental factors
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
Combustible vs. E-cigarettes
Both increase risks of adverse health outcomes
Both expose users to toxic chemicals (smoke and e-vapor)
Vaping increases risk of smoking tobacco cigarettes
Exposure to toxic substances from combustible tobacco cigarettes may be greater than from e-cigarettes
Exposure to metals (e.g., lead, nickel, chromium) may be greater in e-cigarette vapor than tobacco cigarettes
Both are addictive
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
E-liquids AND aerosols contain toxic chemicals
Vaping chemicals can cause DNA damage
Vaping impacts genes, pathways, immune system
Vaping negatively impacts physical and mental health
Vaping increases risk of thousands of diseases
Take Home Points
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
The New Look of Nicotine Addiction (Massachusetts Tobacco Cessation & Prevention Program)
– www.GetOutraged.org
Surgeon General: E-Cigarettes & Young People– www.e-cigarettes.surgeongeneral.gov/
Centers for Disease Control: Electronic Cigarettes– https://www.cdc.gov/tobacco/basic_information/e-
cigarettes/index.htm
Educate Yourself
Resources for HELP
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database
.ORG
Cynthia J Grondin, PhDIlluminating how chemicals affect human health
Comparative Toxicogenomics Database